AB0727 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY OF METHOTREXATE AS REMISSION MAINTENANCE THERAPY AFTER REMISSION-INDUCTION THERAPY WITH TOCILIZUMAB AND GLUCOCORTICOIDS IN SUBJECTS WITH GIANT CELL ARTERITIS (METEORITICS TRIAL): STUDY PROTOCOL
Authors: L. Kreis, W. A. Schmidt, N. Venhoff, C. Dejaco, V. Schäfer
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Giant cell arteritis (GCA) is the most common systemic vasculitis found in adults over 50 years of age and affects medium and large vessels. The standard treatment is glucocorticoids (GC). Because of the negative side effects of GC and the high prevalence of relapses GC should be combined with other immunosuppressive or immunomodulatory agents. Since the GIACTA Trial and other randomized controlled trials (RCT) assigned tocilizumab (TCZ) a GC-sparing effect, higher remission rates compared to placebo and the potency to maintain remission even without GC this biologic is a promising option to treat GCA. Due to the high costs of the TCZ treatment and the increased risk of infections, other treatment options are needed in the long term. An RCT published by Adler et al. showed that only 55% of patients remained in remission after discontinuation of intravenous TCZ therapy. It highlights the need for options to maintain remission after discontinuation of TCZ. The combination of methotrexate (MTX) and GC was also effective in reducing relapse rate and the cumulative GC doses in new or relapsing GCA. <h3>Objectives</h3> The primary objective of the study is to investigate whether MTX is useful for maintaining remission after remission-induction with TCZ and GC in patients with GCA. In addition, we evaluate patient and investigator reported outcomes, prevalence of aortitis, number of vasculitic vessels and change of intima-media-values during the study. <h3>Methods</h3> This monocentric, randomized, double-blind, placebo-controlled study estimates the efficacy of MTX through a treatment period of 12 months and a six-months follow-up. Patients who are in stable remission after treatment with GC and at least six months of treatment with TCZ for new-onset or relapsing giant cell arteritis are eligible for inclusion. Forty participants will be randomly assigned to the treatment arm (N=20) and the placebo arm (N=20). The treatment consists of 17.5 mg MTX subcutaneous weekly for 12 months as a monotherapy. In case of intolerance, elevated liver enzymes or low glomerular filtration rate a dose reduction is possible. In event of relapse an escape treatment with GC on a tapering regimen is added to the study medication. Assessments are conducted eight times during the treatment period and twice during the follow-up. An ultrasound examination takes place on every study visit to measure the intima-media-values of several arteries. Magnetic resonance imaging is performed on baseline, month 12 and 18 to detect aortitis. The primary endpoint is the time to first relapse during the 12 months therapy. Arrows indicate study visits mg, milligram; SC, subcutaneous; BSL, baseline; M, month; GC, glucocorticoids; ULN, upper limit of normal. <h3>Results</h3> No results are available yet. <h3>Conclusion</h3> This is the first study that evaluate MTX as remission maintenance therapy after stable remission has been induced by GC and TCZ in GCA. MTX could be an effective, safe, inexpensive therapy agent after discontinuation of TCZ. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.